Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results: Matched Related, Unrelated, and Alternative Donor Allograft Outcomes for Myeloid and Lymphoid Malignancies
Patients and methods: All patients with AL were transplanted at the Bambino Gesù Children’s Hospital in Rome, Italy, between December 2010 and September 2014; 80 patients were included in group 1, 41 in group 2 and 51 in group 3. Patients were offered α/β T-cell-depleted haplo-HSCT in the absence of suitable conventional donor (HLA identical sibling or 10/10 UD evaluated using high resolution typing) or if affected by rapidly progressive disease not permitting time to identify an UD. Clinical characteristics of patients assigned to the 3 groups and those of their donor are shown in Table1. All children were given a fully myeloablative regimen. No group 1 patient was given any post-transplantation GvHD prophylaxis, while patients of group 2 and 3 were given Cyclosporine-A and short-term methotrexate. Group 1 and 3 patients received ATG Fresenius® (4 mg/Kg/day) from day -5 to -3 for preventing both graft rejection and GvHD.
Results: All group 2 and 3 patients had sustained engraftment of donor cells, while 1 of the 80 patients included in group 1 experienced primary graft failure and was rescued by haplo-HSCT from the other parent. The cumulative incidence (CI) of acute GvHD was 30%, 41% and 42%, respectively. Remarkably, all children of the group 1 who developed acute GvHD had a skin-only involvement, while 17% and 16.3% of those of group 2 and 3 had either gut or liver involvement (p<0.001). The CI of chronic GvHD was significantly lower in group 1 children than in those of groups 2 and 3 (p=0.02, see also Figure 1-Panel A). None of the 4 group 1 patients experiencing chronic GvHD had the extensive form of the disease, while the CI of extensive chronic GvHD of group 2 and 3 was 8% and 14%, respectively (p=0.01). Four, 1 and 6 children of patients assigned in group 1, 2 and 3, respectively, died for transplant-related causes; the CI of transplantation-related mortality (TRM) in the 3 groups is shown in Figure 1-Panel B. Relapse was the main cause of treatment failure and occurred at a comparable CI in all the 3 groups (see also Panel C of Figure 1). The 3-year probability of Event-Free Survival (EFS) was comparable in the 3 groups (Figure 1 - Panel D). In multivariate analysis, a Total Body Irradiation (TBI)-containing regimen was the only variable favourably influencing EFS of group 1 children (hazard ratio 2.93, 95% Confidence Interval 1.24-6.95). No variable influenced EFS of group 2 and 3 patients.
Conclusions: Overall, these data indicate that haplo-HSCT after α/β T-cell depletion is associated with a risk of TRM and leukemia recurrence comparable to that of transplantation from an HLA-identical sibling or an UD, this translating in a similar probability of EFS. In view of the low incidence of chronic GvHD, this transplant option has to be considered a competitive alternative for children with AL in need of an allograft.
|
Sibling (n=41) |
MUD (n=51) |
Haplo (n=80) |
|
Sex |
|
|
|
p=0.77 |
M |
27 |
32 |
55 |
|
F |
14 |
19 |
25 |
|
|
|
|
|
|
Age at Transplantation (years) |
10.6 |
9.4 |
9.7 |
p=0.20 |
Disease |
|
|
|
p=0.23 |
ALL |
34 |
35 |
56 |
|
AML |
7 |
16 |
24 |
|
Disease status at Transplantation |
|
|
|
p=0.13 |
CR1 |
20 |
30 |
30 |
|
CR2 |
21 |
20 |
47 |
|
≥CR3 |
0 |
1 |
3 |
|
CMV serology (Donor/Recipient) |
|
|
|
p=0.001 |
neg/neg |
8 |
5 |
6 |
|
neg/pos |
8 |
21 |
7 |
|
pos/neg |
1 |
4 |
11 |
|
pos/pos |
24 |
21 |
56 |
|
Source of Stem Cells |
|
|
p<0.0001 |
|
BM |
40 |
40 |
0 |
|
PBSC |
1 |
11 |
80 |
|
Conditioning regimens |
|
|
|
p=0.10 |
TBI-based |
26 |
29 |
60 |
|
non TBI-based |
15 |
22 |
20 |
|
Disclosures: No relevant conflicts of interest to declare.
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